ArticleOncotarget2016
Vorinostat and hydroxychloroquine improve immunity and inhibit autophagy in metastatic colorectal cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Modulation of autophagy: a Phase II study of vorinostat plus hydroxychloroquine versus regorafenib in chemotherapy-refractory metastatic colorectal cancer (mCRC).British journal of cancer · 2022Trial
- Challenging the control through a single-cell perspective on normal adjacent tissue in colorectal cancer.iScience · 2026Article
- Unlocking the Epigenetic Landscape of Colorectal Cancer: A Step Toward Epigenetics to Precision.Sub-cellular biochemistry · 2026Review
- Targeting autophagy to enhance cancer immunotherapy: emerging mechanisms and strategies.Medical oncology (Northwood, London, England) · 2025Review
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- A Phase I Trial to Determine the Safety and Tolerability of Autophagy Inhibition Using Chloroquine or Hydroxychloroquine in Combination with Carboplatin and Gemcitabine in Patients with Advanced Solid Tumorsced solid tumors.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance.Expert reviews in molecular medicine · 2024Review
- Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.Heliyon · 2024Review
- The effects of hydroxychloroquine and its promising use in refractory obstetric antiphospholipid syndrome.Rheumatology international · 2024Review
- Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy.International journal of nanomedicine · 2024Review
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Multi-omics characterization of autophagy-related molecular features for therapeutic targeting of autophagy.Nature communications · 2022Article
- A novel senescence-associated LncRNA signature predicts the prognosis and tumor microenvironment of patients with colorectal cancer: a bioinformatics analysis.Journal of gastrointestinal oncology · 2022Article
- Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.Nature communications · 2022Article
- Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.Dermatology and therapy · 2022Review
- Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance.Frontiers in oncology · 2022Review
- A Phase I Trial to Determine the Safety and Tolerability of Autophagy Inhibition Using Chloroquine or Hydroxychloroquine in Combination With Carboplatin and Gemcitabine in Patients With Advanced Solid Tumors.Frontiers in oncology · 2022Article
- Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.Drug discovery today · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hydroxychloroquine (HCQ) enhances the anti-cancer activity of the histone deacetylase inhibitor, vorinostat (VOR), in pre-clinical models and early phase clinical studies of metastatic colorectal cancer (mCRC). Mechanisms could include autophagy inhibition, accumulation of ubiquitinated proteins, and subsequent tumor cell apoptosis. There is growing evidence that autophagy inhibition could lead to improved anti-cancer immunity. To date, effects of autophagy on immunity have not been reported in cancer patients. To address this, we expanded an ongoing clinical study to include patients with advanced, refractory mCRC to evaluate further the clinical efficacy and immune effects of VOR plus HCQ. Refractory mCRC patients received VOR 400 milligrams orally with HCQ 600 milligrams orally daily, in a 3-week cycle. The primary endpoint was median progression-free survival (mPFS). Secondary endpoints include median overall survival (mOS), adverse events (AE), pharmacodynamic of inhibition of autophagy in primary tumors, immune cell analyses, and cytokine levels. Twenty patients were enrolled (19 evaluable for survival) with a mPFS of 2.8 months and mOS of 6.7 months. Treatment-related grade 3-4 AEs occurred in 8 patients (40%), with fatigue, nausea/vomiting, and anemia being the most common. Treatment significantly reduced CD4+CD25hiFoxp3+ regulatory and PD-1+ (exhausted) CD4+ and CD8+ T cells and decreased CD45RO-CD62L+ (naive) T cells, consistent with improved anti-tumor immunity. On-study tumor biopsies showed increases in lysosomal protease cathepsin D and p62 accumulation, consistent with autophagy inhibition. Taken together, VOR plus HCQ is active, safe and well tolerated in refractory CRC patients, resulting in potentially improved anti-tumor immunity and inhibition of autophagy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.